title: Cayman ataxia-related protein is a presynapse-specific caspase-3 substrate.
abstract: Caspase plays an important role in apoptosis and physiological processes such as synaptic plasticity. However, the caspase substrate at the synapse is still unknown. Here we used an in vitro cleavage assay with a small-pool human brain cDNA library. We identified the presynaptic protein Caytaxin as a substrate of caspase-3 and caspase-7. Deficiency in Caytaxin causes Cayman ataxia, a disorder characterized by cerebellar dysfunction and mental retardation. Caytaxin cleavage in cerebellar granule neurons is dependent on caspase-3 activation. The cleavage site is upstream of the cellular retinal and the TRIO guanine exchange factor domain, producing a C-terminal fragment that may play an alternative role in inhibiting MEK2 signaling. Thus, we concluded that Caytaxin is a novel substrate of caspase-3 at the presynapse.
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Itoh
authors.forename: Shimo
authors.initials: S
authors.lastname: Li
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohta
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Hayakawa-Yano
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Eri
authors.initials: E
authors.lastname: Ohta
authors.forename: Akihito
authors.initials: A
authors.lastname: Mizuno
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D048370:MAP Kinase Kinase 2 / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism
chemical_list: C561739:ATCAY protein, human; C518021:Atcay protein, mouse; D009419:Nerve Tissue Proteins; D048370:MAP Kinase Kinase 2; C482129:Map2k2 protein, mouse; D053148:Caspase 3; D053179:Caspase 7